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Abstract

Said A Goueli1,2, Kevin Hsiao1, Marina Zdanovskaia1, and Jolanta Vidugiriene11Promega Corporation Madison, WI 2University of Wisconsin School of Medicine and Public Health, Madison, WI

Cyclic nucleotide phosphodiesterases (PDEs) comprise eleven different gene families of enzymes that are encoded by at least 21 different genes and accounting for at least 55 isoforms. They have been implicated in controlling specific cellular functions including cardiovascular, pulmonary, and inflammatory diseases and they play potential role as targets for treatment of cancer and some other diseases. Inhibition of PDEs was shown to induce chronic lymphocytic leukemia (CLL) apoptosis and more evidence support targeting PDEs for treatments of several types of cancer. Thus, the development of novel isoform-specific inhibitors may be useful for the development of therapeutic agents against cancer. We have development a homogenous PDE-Glo™ Phosphodiesterase Assay for high-throughput screening (HTS) for novel inhibitors of PDE. The HTS formatted assays can be used to monitor the activity of cAMP-PDEs and cGMPPDEs and can be carried out in two simple steps in 96-, 384-, or 1536-well formatted plates. The Assay is luminescent and thus it encounters minimal interference from fluorescent compounds and the robustness of the assays are indicated by their remarkably high Z´ value (>0.8). In summary, the PDE-Glo luminescent assay can be used for screening libraries of compounds targeting in PDEs that might be developed into potential drugs for treatment of cancer and some other diseases.

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